Obstructive sleep apnea endotypes and their postoperative relevance

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms

“…The pathophysiology of OSA is heterogeneous with distinct endotypes, including low arousal threshold, high loop gain, and inadequate upper airway muscle responsiveness during sleep (Figure 1) (Altree & Eckert, 2022; Eckert, 2018; D.J. Eckert et al, 2013).…”

“…Non‐anatomical causes of OSA include a low arousal threshold, high loop gain, and inadequate muscle response during sleep (Figure 1) (Eckert, 2018). While most current treatments for OSA target the upper airway crowding, non‐anatomical OSA endotypes represent novel targets for emerging pharmaceutical research (Altree & Eckert, 2022; Baillieul et al, 2022; Lim et al, 2021; Osman et al, 2023) (Figure 1). As previously described, quetiapine modulates multiple receptor subtypes with variable antagonist or agonist actions.…”

“…This manifests as a high propensity for cortical arousal, or ‘waking up’, to relatively minor respiratory disturbances prior to activation of other compensatory mechanisms. For example, people with a low arousal threshold endotype have fragmented sleep and typically wake up before there is sufficient respiratory stimulus (i.e., negative airway pressure and carbon dioxide [CO 2 ]) to activate upper airway muscles to restore airflow (Altree & Eckert, 2022). Dopamine via the ventral tegmental area in the midbrain influences sleep wake regulation (Oishi & Lazarus, 2017).…”

“…During sleep, the genioglossus, the largest pharyngeal dilator, and other upper airway dilator muscles can compensate for an anatomically crowded, collapsible upper airway to maintain airway patency and adequate airflow (Sands et al, 2014). However, approximately one third of people with OSA have inadequate or poorly coordinated upper airway muscle responses to breathing disturbances during sleep (Altree & Eckert, 2022; Eckert et al, 2013). The 5‐HT2 A receptors provide excitatory input to hypoglossal motor neurones in animal models (Fenik & Veasey, 2003).…”